Effect of Linear Energy Transfer on Cystamine's Radioprotective Activity: A Study Using the Fricke Dosimeter with 6-500 MeV per Nucleon Carbon Ions-Implication for Carbon Ion Hadrontherapy.

(1) Background: Radioprotective agents have garnered considerable interest due to their prospective applications in radiotherapy, public health medicine, and situations of large-scale accidental radiation exposure or impending radiological emergencies. Cystamine, an organic diamino-disulfide compound, is recognized for its radiation-protective and antioxidant properties. This study aims to utilize the aqueous ferrous sulfate (Fricke) dosimeter to measure the free-radical scavenging capabilities of cystamine during irradiation by fast carbon ions. This analysis spans an energy range from 6 to 500 MeV per nucleon, which correlates with "linear energy transfer" (LET) values ranging from approximately 248 keV/µm down to 9.3 keV/µm. (2) Methods: Monte Carlo track chemistry calculations were used to simulate the radiation-induced chemistry of aerated Fricke-cystamine solutions across a broad spectrum of cystamine concentrations, ranging from 10-6 to 1 M. (3) Results: In irradiated Fricke solutions containing cystamine, cystamine is observed to hinder the oxidation of Fe2+ ions, an effect triggered by oxidizing agents from the radiolysis of acidic water, resulting in reduced Fe3+ ion production. Our simulations, conducted both with and without accounting for the multiple ionization of water, confirm cystamine's ability to capture free radicals, highlighting its strong antioxidant properties. Aligning with prior research, our simulations also indicate that the protective and antioxidant efficiency of cystamine diminishes with increasing LET of the radiation. This result can be attributed to the changes in the geometry of the track structures when transitioning from lower to higher LETs. (4) Conclusions: If we can apply these fundamental research findings to biological systems at a physiological pH, the use of cystamine alongside carbon-ion hadrontherapy could present a promising approach to further improve the therapeutic ratio in cancer treatments.

Assessment of Cystamine's Radioprotective/Antioxidant Ability under High-Dose-Rate Irradiation: A Monte Carlo Multi-Track Chemistry Simulation Study.

(1) Background: cystamine and its reduced form cysteamine have radioprotective/antioxidant effects in vivo. In this study, we use an in vitro model system to examine the behavior of cystamine towards the reactive primary species produced during the radiolysis of the Fricke dosimeter under high dose-rate irradiation conditions. (2) Methods: our approach was to use the familiar radiolytic oxidation of ferrous to ferric ions as an indicator of the radioprotective/antioxidant capacity of cystamine. A Monte Carlo computer code was used to simulate the multi-track radiation-induced chemistry of aerated and deaerated Fricke-cystamine solutions as a function of dose rate while covering a large range of cystamine concentrations. (3) Results: our simulations revealed that cystamine provides better protection at pulsed dose rates compared to conventional, low-dose-rate irradiations. Furthermore, our simulations confirmed the radical-capturing ability of cystamine, clearly indicating the strong antioxidant profile of this compound. (4) Conclusion: assuming that these findings can be transposable to cells and tissues at physiological pH, it is suggested that combining cystamine with FLASH-RT could be a promising approach to further enhance the therapeutic ratio of cancer cure.

A Computer Modeling Study of Water Radiolysis at High Dose Rates. Relevance to FLASH Radiotherapy.

"FLASH radiotherapy" is a new method of radiation treatment by which large doses of radiation are delivered at high dose rates to tumors almost instantaneously (a few milliseconds), paradoxically sparing healthy tissue while preserving anti-tumor activity. To date, no definitive mechanism has been proposed to explain the different responses of the tumor and normal tissue to radiation. As a first step, and given that living cells and tissues consist mainly of water, we studied the effects of high dose rates on the transient yields (G values) of the radical and molecular species formed in the radiolysis of deaerated/aerated water by irradiating protons, using Monte Carlo simulations. Our simulation model consisted of two steps: 1. The random irradiation of a right circular cylindrical volume of water, embedded in nonirradiated bulk water, with single and instantaneous pulses of N 300-MeV incident protons ("linear energy transfer" or LET ∼ 0.3 keV/µm) traveling along the axis of the cylinder; and 2. The development of these N proton tracks, which were initially contained in the irradiated cylinder, throughout the solution over time. The effect of dose rate was studied by varying N, which was calibrated in terms of dose rate. For this, experimental data on the yield G(Fe3+) of the super-Fricke dosimeter as a function of dose rate up to ∼1010 Gy/s were used. Confirming previous experimental and theoretical studies, significant changes in product yields were found to occur with increasing dose rate, with lower radical and higher molecular yields, which result from an increase in the radical density in the bulk of the solution. Using the kinetics of the decay of hydrated electrons, a critical time (τc), which corresponds to the "onset" of dose-rate effects, was determined for each value of N. For the cylindrical irradiation model, τc was inversely proportional to the dose rate. Moreover, the comparison with experiments with pulsed electrons underlined the importance of the geometry of the irradiation volume for the estimation of τc. Finally, in the case of aerated water radiolysis, we calculated the yield of oxygen consumption and estimated the corresponding concentration of consumed (depleted) oxygen as a function of time and dose rate. It was shown that this concentration increases substantially with increasing dose rate in the time window ∼1 ns-10 µs, with a very pronounced maximum around 0.2 µs. For high-dose-rate irradiations (>109 Gy/s), a large part of the available oxygen (∼0.25 mM for an air-saturated solution) was found to be consumed. This result, which was obtained on a purely water radiation chemistry basis, strongly supports the hypothesis that the normal tissue-sparing effect of FLASH stems from temporary hypoxia due to oxygen depletion induced by high-dose-rate irradiation.

Ultra-High Dose-Rate, Pulsed (FLASH) Radiotherapy with Carbon Ions: Generation of Early, Transient, Highly Oxygenated Conditions in the Tumor Environment.

It is well known that molecular oxygen is a product of the radiolysis of water with high-linear energy transfer (LET) radiation, which is distinct from low-LET radiation wherein O2 radiolytic yield is negligible. Since O2 is a powerful radiosensitizer, this fact is of practical relevance in cancer therapy with energetic heavy ions, such as carbon ions. It has recently been discovered that large doses of ionizing radiation delivered to tumors at very high dose rates (i.e., in a few milliseconds) have remarkable benefits in sparing healthy tissue while preserving anti-tumor activity compared to radiotherapy delivered at conventional, lower dose rates. This new method is called "FLASH radiotherapy" and has been tested using low-LET radiation (i.e., electrons and photons) in various pre-clinical studies and recently in a human patient. Although the exact mechanism(s) underlying FLASH are still unclear, it has been suggested that radiation delivered at high dose rates spares normal tissue via oxygen depletion. In addition, heavy-ion radiation achieves tumor control with reduced normal tissue toxicity due to its favorable physical depth-dose profile and increased radiobiological effectiveness in the Bragg peak region. To date, however, biological research with energetic heavy ions delivered at ultra-high dose rates has not been performed and it is not known whether heavy ions are suitable for FLASH radiotherapy. Here we present the additive or even synergistic advantages of integrating the FLASH dose rates into carbon-ion therapy. These benefits result from the ability of heavy ions at high LET to generate an oxygenated microenvironment around their track due to the occurrence of multiple (mainly double) ionization of water. This oxygen is abundant immediately in the tumor region where the LET of the carbon ions is very high, near the end of the carbon-ion path (i.e., in the Bragg peak region). In contrast, in the "plateau" region of the depth-dose distribution of ions (i.e., in the normal tissue region), in which the LET is significantly lower, this generation of molecular oxygen is insignificant. Under FLASH irradiation, it is shown that this early generation of O2 extends evenly over the entire irradiated tumor volume, with concentrations estimated to be several orders of magnitude higher than the oxygen levels present in hypoxic tumor cells. Theoretically, these results indicate that FLASH radiotherapy using carbon ions would have a markedly improved therapeutic ratio with greater toxicity in the tumor due to the generation of oxygen at the spread-out Bragg peak.

Yields of primary species in the low-linear energy transfer radiolysis of water in the temperature range of 25-700 °C.

Monte Carlo track chemistry simulations were used to calculate the time-dependent yields (G values) for the radical (eaq-, H˙, ˙OH) and molecular (H2, H2O2) "primary species" formed in the low-linear energy transfer (LET) radiolysis of deaerated, pure water (H2O) in the range of ∼1 ps to 1 ms between 25 and 700 °C, at 25 MPa pressure. Beyond the critical point, we used in the calculations the new supercritical water (SCW) radiolysis database of Liu et al., in particular their reported reaction rate constants. A striking conclusion of these simulations is the sharp increase in G(˙OH) and G(H2), and the corresponding decrease in G(H˙), which are observed above 200 °C, due to the oxidation of water by the H˙ atom (H˙ + H2O → ˙OH + H2) in the homogeneous chemical stage of radiolysis. These results may have important implications for proposed Generation-IV SCW-cooled reactors for the control and management of water chemistry and for the maintenance of the structural integrity of materials.

Radiolysis of supercritical water at 400 °C: density dependence of the rate constant for the reaction of hydronium ions with hydrated electrons.

The rate constant, k(eaq- + H3O+), for the reaction of hydronium ions with hydrated electrons in supercritical water (SCW) at 400 °C has been evaluated as a function of water density using Monte Carlo track chemistry simulations of the radiolysis of SCW over the range of 0.15-0.6 g cm-3. Results are consistent with recent predictions using the so-called "cage effect" model.

Low linear energy transfer radiolysis of supercritical water at 400 °C: in situ generation of ultrafast, transient, density-dependent "acid spikes".

There is growing interest in the radiation chemistry of supercritical water (SCW), as its use as a coolant in a nuclear reactor (Generation IV) is the logical evolution of the current (Generation III or less) water-cooled reactors. However, current knowledge about the potential effects of water radiolysis in a Gen-IV supercritical water-cooled reactor (SCWR) is incomplete. In this work, Monte Carlo track chemistry simulations of the low linear energy transfer (LET) radiolysis of SCW (H2O) at 400 °C are used in combination with a spherical "spur" model to study the effect of water density on the in situ radiolytic formation of H3O+ ions and the corresponding abrupt, transient, highly acidic pH response ("acid spikes") that is observed immediately after irradiation. The magnitude and duration of this acidic pH effect depend on the water density in the considered range of 0.15-0.6 g cm-3. It is strongest at times less than a few tens of picoseconds with the pH remaining nearly constant at ∼1.6 and 1.9 for the highest ("liquid-like") and lowest ("gas-like") density, respectively. At longer times, the pH gradually increases for all densities and finally reaches a constant value corresponding to the non-radiolytic, pre-irradiation concentration of H3O+, due to the autoprotolysis of water. Our results show that the lower the density of the water, the longer the time required to reach this constant value, ranging from ∼50 ns at 0.6 g cm-3 (pH ∼ 5.6) to ∼1 µs at 0.15 g cm-3 (pH ∼ 8.5). The generation of these highly acidic pH fluctuations around the "native" radiation tracks, though local and transient, raises questions about the potential implications of this effect in proposed Gen-IV SCW-cooled reactors regarding corrosion and degradation of materials.

Self-radiolysis of tritiated water. 4. The scavenging effect of azide ions (N3 -) on the molecular hydrogen yield in the radiolysis of water by 60Co γ-rays and tritium ß-particles at room temperature.

The effect of the azide ion N3 - on the yield of molecular hydrogen in water irradiated with 60Co γ-rays (∼1 MeV Compton electrons) and tritium ß-electrons (mean electron energy of ∼7.8 keV) at 25 °C is investigated using Monte Carlo track chemistry simulations in conjunction with available experimental data. N3 - is shown to interfere with the formation of H2 through its high reactivity towards hydrogen atoms and, but to a lesser extent, hydrated electrons, the two major radiolytic precursors of the H2 yield in the diffusing radiation tracks. Chemical changes are observed in the H2 scavengeability depending on the particular type of radiation considered. These changes can readily be explained on the basis of differences in the initial spatial distribution of primary radiolytic species (i.e., the structure of the electron tracks). In the "short-track" geometry of the higher "linear energy transfer" (LET) tritium ß-electrons (mean LET ∼5.9 eV nm-1), radicals are formed locally in much higher initial concentration than in the isolated "spurs" of the energetic Compton electrons (LET ∼0.3 eV nm-1) generated by the cobalt-60 γ-rays. As a result, the short-track geometry favors radical-radical reactions involving hydrated electrons and hydrogen atoms, leading to a clear increase in the yield of H2 for tritium ß-electrons compared to 60Co γ-rays. These changes in the scavengeability of H2 in passing from tritium ß-radiolysis to γ-radiolysis are in good agreement with experimental data, lending strong support to the picture of tritium ß-radiolysis mainly driven by the chemical action of short tracks of high local LET. At high N3 - concentrations (>1 M), our H2 yield results for 60Co γ-radiolysis are also consistent with previous Monte Carlo simulations that suggested the necessity of including the capture of the precursors to the hydrated electrons (i.e., the short-lived "dry" electrons prior to hydration) by N3 -. These processes tend to reduce significantly the yields of H2, as is observed experimentally. However, this dry electron scavenging at high azide concentrations is not seen in the higher-LET 3H ß-radiolysis, leading us to conclude that the increased amount of intra-track chemistry intervening at early time under these conditions favors the recombination of these electrons with their parent water cations at the expense of their scavenging by N3 -.

Modeling the radiolysis of supercritical water by fast neutrons: density dependence of the yields of primary species at 400°c.

A reliable understanding of radiolysis processes in supercritical water (SCW)-cooled reactors is crucial to developing chemistry control strategies that minimize the corrosion and degradation of materials. However, directly measuring the chemistry in reactor cores is difficult due to the extreme conditions of high temperature and pressure and mixed neutron and gamma-radiation fields, which are incompatible with normal chemical instrumentation. Thus, chemical models and computer simulations are an important route of investigation for predicting the detailed radiation chemistry of the coolant in a SCW reactor and the consequences for materials. Surprisingly, information on the fast neutron radiolysis of water at high temperatures is limited, and even more so for fast neutron irradiation of SCW. In this work, Monte Carlo simulations were used to predict the G values for the primary species e(-)aq, H(•), H2, (•)OH and H2O2 formed from the radiolysis of pure, deaerated SCW (H2O) by 2 MeV monoenergetic neutrons at 400°C as a function of water density in the range of ∼0.15-0.6 g/cm(3). The 2 MeV neutron was taken as representative of a fast neutron flux in a reactor. For light water, the moderation of these neutrons after knock-on collisions with water molecules generated mostly recoil protons of 1.264, 0.465, 0.171 and 0.063 MeV. Neglecting oxygen ion recoils and assuming that the most significant contribution to the radiolysis came from these first four recoil protons, the fast neutron yields were estimated as the sum of the G values for these protons after appropriate weightings were applied according to their energy. Calculated yields were compared with available experimental data and with data obtained for low-LET radiation. Most interestingly, the reaction of H(•) atoms with water was found to play a critical role in the formation yields of H2 and (•)OH at 400°C. Recent work has underscored the potential importance of this reaction above 200°C, but its rate constant is still controversial.

Calculation of the yields for the primary species formed from the radiolysis of liquid water by fast neutrons at temperatures between 25-350°C.

Monte Carlo simulations were used to calculate the yields for the primary species (e(-)aq, H(•), H2, (•)OH and H2O2) formed from the radiolysis of neutral liquid water by mono-energetic 2 MeV neutrons at temperatures between 25-350°C. The 2 MeV neutron was taken as representative of a fast neutron flux in a reactor. For light water, the moderation of these neutrons generated elastically scattered recoil protons of ∼1.264, 0.465, 0.171 and 0.063 MeV, which at 25°C, had linear energy transfers (LETs) of ∼22, 43, 69 and 76 keV/µm, respectively. Neglecting the radiation effects due to oxygen ion recoils and assuming that the most significant contribution to the radiolysis came from these first four recoil protons, the fast neutron yields could be estimated as the sum of the yields for these protons after allowance was made for the appropriate weightings according to their energy. Yields were calculated at 10(-7), 10(-6) and 10(-5) s after the ionization event at all temperatures, in accordance with the time range associated with the scavenging capacities generally used for fast neutron radiolysis experiments. The results of the simulations agreed reasonably well with the experimental data, taking into account the relatively large uncertainties in the experimental measurements, the relatively small number of reported radiolysis yields, and the simplifications included in the model. Compared with data obtained for low-LET radiation ((60)Co γ rays or fast electrons), our computed yields for fast neutron radiation showed essentially similar temperature dependences over the range of temperatures studied, but with lower values for yields of free radicals and higher values for molecular yields. This general trend is a reflection of the high-LET character of fast neutrons. Although the results of the simulations were consistent with the experiment, more experimental data are required to better describe the dependence of radiolytic yields on temperature and to test more thoroughly our modeling calculations.

Effect of temperature on the low-linear energy transfer radiolysis of the ceric-cerous sulfate dosimeter: a Monte Carlo simulation study.

The stochastic modeling of the (60)Co γ/fast-electron radiolysis of the ceric-cerous chemical dosimeter has been performed as a function of temperature from 25-350°C. The system used is a dilute solution of ceric sulfate and cerous sulfate in aqueous 0.4 M sulfuric acid. In this system, H(•) (or HO2(•) in the presence of dissolved oxygen) and H2O2 produced by the radiolytic decomposition of water both reduce Ce(4+) ions to Ce(3+) ions, while (•)OH radicals oxidize the Ce(3+) present in the solution back to Ce(4+). The net Ce(3+) yield is given by G(Ce(3+)) = g(H(•)) + 2 g(H2O2) - g((•)OH), where the primary (or "escape") yields of H(•), H2O2 and (•)OH are represented by lower case g's. At room temperature, G(Ce(3+)) has been established to be 2.44 ± 0.8 molecules/100 eV. In this work, we investigated the effect of temperature on the yield of Ce(3+) and on the underlying chemical reaction kinetics using Monte Carlo track chemistry simulations. The simulations showed that G(Ce(3+)) is time dependent, a result of the differences in the lifetimes of the reactions that make up the radiolysis mechanism. Calculated G(Ce(3+)) values were found to decrease almost linearly with increasing temperature up to about 250°C, and are in excellent agreement with available experimental data. In particular, our calculations confirmed previous estimated values by Katsumura et al. (Radiat Phys Chem 1988; 32:259-63) showing that G(Ce(3+)) at ∼250°C is about one third of its value at room temperature. Above ∼250°C, our model predicted that G(Ce(3+)) would drop markedly with temperature until, instead of Ce(4+) reduction, Ce(3+) oxidation is observed. This drop is shown to occur as a result of the reaction of hydrogen atoms with water in the homogeneous chemical stage.

Density dependence of the yield of hydrated electrons in the low-LET radiolysis of supercritical water at 400 °C: influence of the geminate recombination of subexcitation-energy electrons prior to thermalization.

Monte Carlo simulations were used to calculate the yield of hydrated electrons (eaq(-)) in the low-linear energy transfer radiolysis of supercritical water at 400 °C as a function of water density over the range of ~0.15 to 0.6 g cm(-3). Very good agreement was found between our calculations and picosecond pulse radiolysis experimental data at ~60 ps and 1 ns at high density (>0.35 g cm(-3)). At densities lower than ~0.35 g cm(-3), our eaq(-) yields were lower than the experimental data, especially at ~60 ps. However, if we incorporated into the simulations a prompt geminate electron-cation (H2O˙(+)) recombination (prior thermalization of the electron) that decreased as the density decreased, our computed eaq(-) yields at ~60 ps and 1 ns compared fairly well with the experimental data for the entire density range studied.

On the spur lifetime and its temperature dependence in the low linear energy transfer radiolysis of water.

In the spirit of the radiation chemical "spur model", the lifetime of a spur (τ(s)) is an important indicator of overlapping spurs and the establishment of homogeneity in the distribution of reactive species created by the action of low linear energy transfer (LET) radiation (such as fast electrons or γ irradiation). In fact, τ(s) gives the time required for the changeover from nonhomogeneous spur kinetics to homogeneous kinetics in the bulk solution, thus defining the so-called primary (or "escape") radical and molecular yields of radiolysis, which are obviously basic to the quantitative understanding of any irradiated chemical system. In this work, τ(s) and its temperature dependence have been determined for the low-LET radiolysis of deaerated 0.4 M aqueous solutions of H(2)SO(4) and pure liquid water up to 350 °C using a simple model of energy deposition initially in spurs, followed by random diffusion of the species of the spur during track expansion until spur overlap is complete. Unlike our previous τ(s) calculations, based on irradiated Fricke dosimeter simulations, the current model is free from any effects due to the presence of oxygen or the use of scavengers. In acidic solutions, the spur lifetime values thus obtained are in very good agreement with our previous calculations (after making appropriate corrections, however, to account for the possibility of competition between oxygen and Fe(2+) ions for H˙ atoms in the Fricke dosimeter, an effect which was not included in our original simulations). In this way, we confirm the validity of our previous approach. As expected, in the case of pure, oxygen-free water, our calculated times required to reach complete spur overlap are essentially the same (within uncertainty limits) as those found in acidic solutions. This explicitly reflects the fact that the diffusion coefficients for the hydrated electron and the H˙ atom that are involved in the overall calculation of the lifetime of spurs in neutral or acidic media, respectively, are of similar magnitude over the 25-350 °C temperature range studied.

Time-dependent yield of the hydrated electron in subcritical and supercritical water studied by ultrafast pulse radiolysis and Monte-Carlo simulation.

Fast kinetics and time-dependent yields of the hydrated electron (e(-)(aq)) in pure water under conditions of high temperature and pressure up to the supercritical region were investigated by picosecond and nanosecond pulse radiolysis experiments. More significant decays at short times followed by plateau components at longer times were observed with increasing temperature, suggesting faster spur reaction processes. In supercritical water, it was also found that the e(-)(aq) yields strongly depend on the pressure (density). Comparison of these measurements with Monte-Carlo computer simulations allowed us to identify spur reactions of e(-)(aq) that occur predominantly at high temperatures and also to provide new key information on certain spur model parameters. In particular, the experimental time-dependent e(-)(aq) yields were best reproduced if the electron thermalization distance decreases with increasing temperature. This "shrinkage" of spur sizes at high temperatures was attributed to an increase in the scattering cross sections of subexcitation electrons, likely originating from a decrease in the degree of structural order of water molecules as the temperature is increased.

Density dependence of the "escape" yield of hydrated electrons in the low-LET radiolysis of supercritical water at 400 °C.

The "spur lifetime" (τ(s)) in the low-linear energy transfer (LET) radiolysis of supercritical water (SCW) at 400 °C has been determined as a function of water density by using a simple model of energy deposition initially in spurs, followed by the random diffusion (Brownian motion) of the species formed until spur expansion is complete. The values of τ(s) are found to decrease from ∼5.0 × 10(-6) to 5.0 × 10(-8) s over the density range from 0.15 to 0.6 g cm(-3). Using Monte-Carlo simulations, our calculated density dependence of the "escape" hydrated electron (e(aq)(-)) yield (i.e., at time τ(s)) reproduces fairly well Bartels and co-workers' scavenged e(aq)(-) yield data, suggesting that these data may have been measured at times close to τ(s).

Utilization of the ferrous sulfate (Fricke) dosimeter for evaluating the radioprotective potential of cystamine: experiment and Monte Carlo simulation.

Cystamine, an organic disulfide (RSSR), is among the best of the known radiation-protective compounds and has been used to protect normal tissues in clinical radiation therapy. Recently, it has also proved to be beneficial in the treatment of disorders of the central nervous system in animal models. However, the underlying mechanism of its action at the chemical level is not yet well understood. The present study aims at using the ferrous sulfate (Fricke) dosimeter to quantitatively evaluate, both experimentally and theoretically, the radioprotective potential of this compound. The well-known radiolysis of the Fricke dosimeter by (60)Co γ rays or fast electrons, based on the oxidation of ferrous ions to ferric ions by the oxidizing species (•)OH, HO(2)(•), and H(2)O(2) produced in the radiolytic decomposition of water, forms the basis for our method. The presence of cystamine in Fricke dosimeter solutions during irradiation prevents the radiolytic oxidation of Fe(2+) and leads to decreased ferric yields (or G values). The observed decrease in G(Fe(3+)) increases upon increasing the concentration of the disulfide compound over the range 0-0.1 M under both aerated and deaerated conditions. To help assess the basic radiation-protective mechanism of this compound, a full Monte Carlo computer code is developed to simulate in complete detail the radiation-induced chemistry of the studied Fricke/cystamine solutions. Benefiting from the fact that cystamine is reasonably well characterized in terms of radiation chemistry, this computer model proposes reaction mechanisms and incorporates specific reactions describing the radiolysis of cystamine in aerated and deaerated Fricke solutions that lead to the observable quantitative chemical yields. Results clearly indicate that the protective effect of cystamine originates from its radical-capturing ability, which allows this compound to act by competing with the ferrous ions for the various free radicals--especially (•)OH radicals and H(•) atoms--formed during irradiation of the surrounding water. Most interestingly, our simulation modeling also shows that the predominant pathway in the oxidation of cystamine by (•)OH radicals involves an electron-transfer mechanism, yielding RSSR(•+) and OH(-). A very good agreement is found between calculated G(Fe(3+)) values and experiment. This study concludes that Monte Carlo simulations represent a very efficient method for understanding indirect radiation damage at the molecular level.

Temperature dependence of the Fricke dosimeter and spur expansion time in the low-LET high-temperature radiolysis of water up to 350 °C: a Monte-Carlo simulation study.

Monte-Carlo simulations of the radiolysis of the ferrous sulfate (Fricke) dosimeter with low-linear energy transfer (LET) radiation (such as (60)Co γ-rays or fast electrons) have been performed as a function of temperature from 25 to 350 °C. The predicted yields of Fe(2+) oxidation are found to increase with increasing temperature up to ∼100-150 °C, and then tend to remain essentially constant at higher temperatures, in very good agreement with experiment. By using a simple method based on the direct application of the stoichiometric relationship that exists between the ferric ion yields so obtained G(Fe(3+)) and the sum {3 [g(e(-)(aq) + H˙) + g(HO(2)˙)] + g(˙OH) + 2 g(H(2)O(2))}, where g(e(-)(aq) + H˙), g(HO(2)˙), g(˙OH), and g(H(2)O(2)) are the primary radical and molecular yields of the radiolysis of deaerated 0.4 M H(2)SO(4) aqueous solutions, the lifetime (τ(s)) of the spur and its temperature dependence have been determined. In the spirit of the spur model, τ(s) is an important indicator for overlapping spurs, giving the time required for the changeover from nonhomogeneous spur kinetics to homogeneous kinetics in the bulk solution. The calculations show that τ(s) decreases by about an order of magnitude over the 25-350 °C temperature range, going from ∼4.2 × 10(-7) s at 25 °C to ∼5.7 × 10(-8) s at 350 °C. This decrease in τ(s) with increasing temperature mainly originates from the quicker diffusion of the individual species involved. Moreover, the observed dependence of G(Fe(3+)) on temperature largely reflects the influence of temperature upon the primary free-radical product yields of the radiolysis, especially the yield of H˙ atoms. Above ∼200-250 °C, the more and more pronounced intervention of the reaction of H˙ atoms with water also contributes to the variation of G(Fe(3+)), which may decrease or increase slightly, depending on the choice made for the rate constant of this reaction. All calculations reported herein use the radiolysis database of Elliot (Atomic Energy of Canada Limited) and Bartels (University of Notre Dame) that contains all the best currently available information on the rate constants, reaction mechanisms, and g-values in the range 20 to 350 °C.

High-LET ion radiolysis of water: oxygen production in tracks.

It is known that molecular oxygen is a product of the radiolysis of water with high-linear energy transfer (LET) radiation, a result that is of particular significance in radiobiology and of practical relevance in radiotherapy. In fact, it has been suggested that the radiolytic formation of an oxygenated microenvironment around the tracks of high-LET heavy ions is an important factor in their enhanced biological efficiency in the sense that this may be due to an "oxygen effect" by O(2) produced by these ions in situ. Using Monte Carlo track simulations of pure, deaerated water radiolysis by 4.8 MeV (4)He(2+) (LET approximately 94 keV/microm) and 24 MeV (12)C(6+) (LET approximately 490 keV/microm) ions, including the mechanism of multiple ionization of water, we have calculated the yields and concentrations of O(2) in the tracks of these irradiating ions as a function of time between approximately 10(-12) and 10(-5) s at 25 and 37 degrees C. The track oxygen concentrations obtained compare very well with O(2) concentrations estimated from the "effective" amounts of oxygen that are needed to produce the observed reduction in oxygen enhancement ratio (OER) with LET (assuming this decrease is attributable to the sole radiolytic formation of O(2) in the tracks). For example, for 24 MeV (12)C(6+) ions, the initial track concentration of O(2) is estimated to be more than three orders of magnitude higher than the oxygen levels present in normally oxygenated and hypoxic tumor regions as well as in normal human cells. Such results, which largely plead in favor of the "oxygen in the heavy-ion track" hypothesis, could explain at least in part the greater efficiency of high-LET radiation for cell inactivation (at equal radiation dose).

Effect of water density on the absorption maximum of hydrated electrons in sub- and supercritical water up to 400 degrees C.

The optical absorption spectra of the hydrated electron (e(aq) (-)) in supercritical (heavy) water (SCW) are measured by electron pulse radiolysis techniques as a function of water density at three temperatures of 380, 390, and 400 degrees C, and over the density range of approximately 0.2-0.65 g/cm(3). In agreement with previous work, the position of the e(aq) (-) absorption maximum (E(A(max) )) is found to shift slightly to lower energies (spectral "redshift") with decreasing density. A comparison of the present E(A(max) )-density data with other measurements already reported in the literature in subcritical (350 degrees C) and supercritical (375 degrees C) water reveals that at a fixed pressure, E(A(max) ) decreases monotonically with increasing temperature in passing through the phase transition at t(c). By contrast, at constant density, E(A(max) ) exhibits a minimum as the water passes above the critical point into SCW. These behaviors are explained in terms of simple microscopic arguments based on the crucial role played by local density and configurational fluctuations (associated with criticality) in providing pre-existing polymeric clusters, which act as trapping sites for electrons.